Following subcutaneous injection, radiolabeled monoclonal antibodies bind efficiently to normal and tumor target cells in the lymph nodes. This finding prompted us to attempt specific therapy using monoclonal antibodies covalently coupled to plant toxins. The first development along these lines has been to synthesize monoclonal antibody-ricin A-chain conjugates using four antibodies of different specificities. We then demonstrated the capacity of these conjugates to bind to their target cells and to inhibit protein synthesis at the ribosomal level in an acellular system. The cytotoxicity of these conjugates for target cells is currently under test. Using the guinea pig hepatocarcinoma cell line (L 10), which expresses large quantities of target antigen, we found only weak cytotoxicity with the monoclonal antibody D3 coupled to ricin A-chain. However, the same toxin coupled to an anti-mouse MHC antibody has proved to be highly toxic for lymphoid cells; similar results are expected with the other conjugates. Another approach to specific therapy within the lymphatic system is the subcutaneous injection of a monoclonal antibody followed by a similar injection of complement. Such a system attempts to reproduce physiological antibody/complement dependent cytotoxicity. The determination of optimal doses and injection regimes will be facilitated by our current studies on monoclonal antibody pharmacokinetics and by in vitro cytotoxicity assays.